Trafficking-defective mutant PROKR2 cycles between endoplasmic reticulum and Golgi to attenuate endoplasmic reticulum stress
| العنوان: | Trafficking-defective mutant PROKR2 cycles between endoplasmic reticulum and Golgi to attenuate endoplasmic reticulum stress |
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| المؤلفون: | Yong Bhum Song, Seung-Yeol Park, Kunyou Park, Hayoung Hwang, Rona S. Carroll, Victor W. Hsu, Ursula B. Kaiser |
| المصدر: | Proceedings of the National Academy of Sciences. 119 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Multidisciplinary, Receptors, Peptide, Hypogonadism, Cell Membrane, Mutation, Missense, Golgi Apparatus, Endoplasmic Reticulum-Associated Degradation, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Receptors, G-Protein-Coupled, Protein Transport, HEK293 Cells, COS Cells, Chlorocebus aethiops, Proteostasis, Animals, Humans, HeLa Cells, Signal Transduction |
| الوصف: | G protein-coupled receptors (GPCRs) play crucial roles in numerous physiological and pathological processes. Mutations in GPCRs that result in loss of function or alterations in signaling can lead to inherited or acquired diseases. Herein, studying prokineticin receptor 2 (PROKR2), we initially identify distinct interactomes for wild-type (WT) versus a mutant (P290S) PROKR2 that causes hypogonadotropic hypogonadism. We then find that both the WT and mutant PROKR2 are targeted for endoplasmic reticulum (ER)-associated degradation, but the mutant is degraded to a greater extent. Further analysis revealed that both forms can also leave the ER to reach the Golgi. However, whereas most of the WT is further transported to the cell surface, most of the mutant is retrieved to the ER. Thus, the post-ER itinerary plays an important role in distinguishing the ultimate fate of the WT versus the mutant. We have further discovered that this post-ER itinerary reduces ER stress induced by the mutant PROKR2. Moreover, we extend the core findings to another model GPCR. Our findings advance the understanding of disease pathogenesis induced by a mutation at a key residue that is conserved across many GPCRs and thus contributes to a fundamental understanding of the diverse mechanisms used by cellular quality control to accommodate misfolded proteins. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36f327089086f7799ad2953e8009abdd https://doi.org/10.1073/pnas.2102248119 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....36f327089086f7799ad2953e8009abdd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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